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A Functionalized 20‐Residue Peptaibol Derivative for Nucleic Acid Delivery
Author(s) -
Wada Shunichi,
Tanaka Reiko
Publication year - 2007
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200790090
Subject(s) - peptide , chemistry , oligonucleotide , fibroblast , nucleic acid , a549 cell , confocal microscopy , membrane , amino acid , fluorescence microscope , cell penetrating peptide , biochemistry , biophysics , cell , fluorescence , microbiology and biotechnology , dna , in vitro , biology , physics , quantum mechanics
Based on the membrane‐modifying peptaibol trichocellin‐A‐I ( 1 ) from Trichoderma viride , we designed a vehicle for the cellular delivery of antisense oligodeoxynucleotides by attaching a (Lys) 10 stretch to the C‐terminus of 1 . The resulting transporter peptide 2 , prepared by solid‐phase synthesis using Fmoc protocol in combination with amino acid fluorides, was found to be mainly α ‐helical in solution, in contrast to its precursors 1 and 3 . The uptake of the complex formed between carrier 2 and a fluorescence‐tagged oligonucleotide, i.e. , 4 , was studied at different charge ratios by confocal laser‐scanning microscopy, using two different eukaryotic cell lines: mouse embryonal fibroblast (NIH3T3) and human lung carcinoma (A549) cells. Peptide 2 readily translocated 4 into the cytoplasms of NIH3T3 cells. However, the peptide/oligonucleotide complex was accumulated around the plasma membrane of the A549 cells.